The plan is to develop experimental evidence in both animal and human model systems which will enable us to answer the fundamental question "Is the selective activation of embryonic genes a necessary step in neoplastic transformation?" Initially, the effort will be directed towards determining which embryonic proteins and their chromosomal loci should be studied and towards perfecting conditions for studying embryonic gene expression during transformation induced by DNA and RNA viruses and by hormones. Simultaneously, the control of embryonic gene expression will be investigated in established cell lines and evidence for the extent of embryonic gene activation in selected patient populations will be gathered. The results of the initial effort should answer a relevant question, namely "What is the nature and extent of embryonic gene activation in neoplastic transformation and in neoplasia?" Once this information is obtained, we would be in a position to select for study the particular embryonic genes whose activation is considered necessary for the process of neoplastic transformation. We would also be in a position to examine the controls which regulate the expression of these particular genes and to measure the corresponding embryonic gene products in patients who are expected to be undergoing the connected events of neoplastic transformation and neoplasia. In the course of these studies, we expect to establish more clearly the relationship of viral and host genomes, the effect of estrogens on malignant transformation, and to identify and quantitate additional clinically useful cancer cell phenotypes in melanoma, medullary thyroid carcinoma, bronchogenic cancer, ovarian cancer and cancer of the gastrointestinal tract.